scholarly journals Expression of Tumor Necrosis Factor-Alpha and Intercellular Adhesion Molecule-1 after Focal Cerebral Ischemia in Interleukin-1β Converting Enzyme Deficient Mice

1999 ◽  
Vol 19 (10) ◽  
pp. 1109-1117 ◽  
Author(s):  
Guo-Yuan Yang ◽  
Gerald P. Schielke ◽  
Chao Gong ◽  
Ying Mao ◽  
Hai-Liang Ge ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Ipsilateral Hemisphere ◽  
Ischemic Brain ◽  
Tnf Α ◽  
Factor Alpha

Interleukin-1β (IL-1β) is expressed after cerebral ischemia and blocking its action reduces subsequent ischemic brain injury. However, the mechanisms by which IL-1β affects ischemic brain are not understood. To investigate the role of IL-1β in regulation of tumor necrosis factor-alpha (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) during focal cerebral ischemia, the authors studied mutant mice deficient in the IL-1 converting enzyme (ICE) gene (ICE knockout [KO] mice). Ninety-four adult male ICE KO and wild-type mice underwent 3, 6, 12, and 24 hours of permanent middle cerebral artery occlusion using the suture method. Expression of TNF-α and ICAM-1 protein in ischemic brain was examined using immunohistochemistry and Western blot analysis. Neither ICE KO nor wild-type mice had significant differences in CBF and body temperature measurements during the ischemic procedure. TNF-α expression increased in the ipsilateral hemisphere after 3 hours of occlusion, peaked at 12 hours and decreased at 24 hours of ischemia in both ICE KO and wild-type mice. ICAM-1 immunohistochemistry showed that the number of ICAM-1–positive vessels in the ischemic hemisphere was reduced in ICE KO mice ( P < .05). Western blot analysis showed that ICAM-1 protein expression was significantly attenuated in the ipsilateral hemisphere in the ICE KO mice, which paralleled the immunohistochemistry results, The authors' results indicate that TNF-α expression is increased in both ICE KO and wild-type mice suggesting that TNF-α expression is not related to or upregulated by IL-1β. ICAM-1 expression is significantly reduced in the ICE KO mice suggesting that IL-1β plays an important role in the upregulation of adhesion molecules during focal cerebral ischemia.

scholarly journals Deficiency of Intercellular Adhesion Molecule 1 Attenuates Microcirculatory Disturbance and Infarction Size in Focal Cerebral Ischemia

1998 ◽  
Vol 18 (12) ◽  
pp. 1336-1345 ◽  
Author(s):  
Kazuo Kitagawa ◽  
Masayasu Matsumoto ◽  
Takuma Mabuchi ◽  
Yoshiki Yagita ◽  
Toshiho Ohtsuki ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Knockout Mice ◽  
Focal Cerebral Ischemia ◽  
Focal Ischemia ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1 ◽  
Transient Focal Ischemia

Recent evidence has shown crucial roles for cell-adhesion molecules in inflammation-induced rolling, adhesion, and accumulation of neutrophils in tissue. Intercellular adhesion molecule-1 (ICAM-1) is one of these adhesion molecules. Previous studies have shown marked reduction in the size of infarction after focal cerebral ischemia by depletion of granulocytes and administration of the antibody against ICAM-1. In the present study we investigated the role of ICAM-1 in the size of ischemic lesions, accumulation of granulocytes, and microcirculatory compromise in focal cerebral ischemia by using ICAM-1–knockout mice. Ischemic lesions were significantly mitigated in knockout mice after permanent and transient focal ischemia, even though the number of granulocytes in the infarcted tissue was almost the same between knockout and wild-type mice. Depletion of granulocytes further decreased the size of ischemic lesions after transient focal ischemia in ICAM-1–knockout mice. Microcirculation was reduced after focal ischemia, but it was better preserved in the cerebral cortex of knockout mice than that of wild-type mice. The present study demonstrated that ICAM-1 played a role in microcirculatory failure and subsequent development and expansion of infarction after focal cerebral ischemia. However, it is highly unlikely that ICAM-1 played a key role in accumulation of granulocytes after focal cerebral ischemia.

scholarly journals Cryptococcal Glucuronoxylomannan Inhibits Adhesion of Neutrophils to Stimulated Endothelium In Vitro by Affecting Both Neutrophils and Endothelial Cells

2002 ◽  
Vol 70 (9) ◽  
pp. 4762-4771 ◽  
Author(s):  
Pauline M. Ellerbroek ◽  
Andy I. M. Hoepelman ◽  
Floor Wolbers ◽  
Jaap Jan Zwaginga ◽  
Frank E. J. Coenjaerts
Keyword(s):  
Capsular Polysaccharide ◽  
Inhibitory Effect ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Blocking Antibodies ◽  
Selectin Binding

ABSTRACT Cryptococcal infections are often characterized by a paucity of leukocytes in the infected tissues. Previous research has shown that the capsular polysaccharide glucuronoxylomannan (GXM) inhibits leukocyte migration. In this study we investigated whether the capsular polysaccharide GXM affects the migration of neutrophils (polymorphonuclear leukocytes [PMN]) through the endothelium by interfering with adhesion in a static adhesion model. Pretreatment of PMN with GXM inhibited PMN adhesion to tumor necrosis factor alpha (TNF-α)-stimulated endothelium up to 44%. Treatment of TNF-α-stimulated endothelium with GXM led to a 27% decrease in PMN adhesion. GXM treatment of both PMN and endothelium did not have an additive inhibitory effect. We demonstrated that GXM-induced L-selectin shedding does not play an important role in the detected inhibition of adhesion. L-selectin was still present on PMN in sufficient amounts after GXM treatment, since it could be further inhibited by blocking antibodies. Furthermore, blocking of GXM-related L-selectin shedding did not abolish the GXM-related inhibition of adhesion. GXM most likely exerts its effect on PMN by interfering with E-selectin-mediated binding. The use of blocking monoclonal antibodies against E-selectin, which was shown to decrease adhesion in the absence of GXM, did not cause additive inhibition of PMN adhesion after GXM pretreatment. The use of blocking antibodies also demonstrated that the inhibiting effect found after GXM treatment of endothelium probably involves interference with both intercellular adhesion molecule-1 and E-selectin binding.

scholarly journals Tumor Necrosis Factor Alpha-Induced Apoptosis Requires p73 and c-ABL Activation Downstream of RB Degradation

2004 ◽  
Vol 24 (10) ◽  
pp. 4438-4447 ◽  
Author(s):  
B. Nelson Chau ◽  
Tung-Ti Chen ◽  
Yisong Y. Wan ◽  
James DeGregori ◽  
Jean Y. J. Wang
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Abl Tyrosine Kinase ◽  
Tnf Α ◽  
Factor Alpha ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT The retinoblastoma protein (RB) suppresses cell proliferation and apoptosis. We have previously shown that RB degradation is required for tumor necrosis factor alpha (TNF-α) to induce apoptosis. We show here the identification of two apoptotic effectors, i.e., c-ABL tyrosine kinase and p73, which are activated by TNF-α following RB degradation. In cells expressing a degradation-resistant RB protein (RB-MI), TNF-α does not activate c-ABL. RB-MI also inhibits TNF-α-mediated activation of p73. Genetic deletion and pharmacological inhibition of c-ABL or p73 diminish the apoptotic response to TNF-α in human cell lines and mouse fibroblasts. Thymocytes isolated from RbMI/MI , Abl −/−, or p73 −/− mice are resistant to TNF-α-induced apoptosis compared to their wild-type counterparts. This is in contrast to p53 −/− thymocytes, which exhibit a wild-type level of apoptosis in response to TNF-α. Thus, c-ABL and p73 contribute to apoptosis induced by TNF-α, in addition to their role in promoting DNA damage-associated cell death.

Nuclear Factor κB and Anesthetic Preconditioning during Myocardial Ischemia-Reperfusion

2004 ◽  
Vol 100 (3) ◽  
pp. 540-546 ◽  
Author(s):  
Caiyun Zhong ◽  
Yamei Zhou ◽  
Hong Liu
Keyword(s):  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Nuclear Factor ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Nf Kappab ◽  
Myocardial Ischemia Reperfusion ◽  
Oxide Synthase

Background Volatile anesthetic preconditioning (APC) protects against myocardial ischemia-reperfusion (IR) injury, but the precise mechanisms underlying this phenomenon remain undefined. To investigate the molecular mechanism of APC in myocardial protection, the activation of nuclear factor (NF) kappaB and its regulated inflammatory mediators expression were examined in the current study. Methods Hearts from male rats were isolated, Langendorff perfused, and randomly assigned to one of three groups: (1) the control group: hearts were continuously perfused for 130 min; (2) the IR group: 30 min of equilibration, 15 min of baseline, 25 min of ischemia, 60 min of reperfusion; and (3) the APC + IR group: 30 min of equilibration, 10 min of sevoflurane exposure and a 5-min washout, 25 min of global ischemia, 60 min of reperfusion. Tissue samples were acquired at the end of reperfusion. NF-kappaB activity was determined by electrophoretic mobility shift assay. The NF-kappaB inhibitor, IkappaB-alpha, was determined by Western blot analysis. Myocardial inflammatory mediators, including tumor necrosis factor alpha, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase, were also assessed by Western blot analysis. Results Nuclear factor kappaB-DNA binding activity was significantly increased at the end of reperfusion in rat myocardium, and cytosolic IkappaB-alpha was decreased. Supershift assay revealed the involvement of NF-kappaB p65 and p50 subunits. APC with sevoflurane attenuated NF-kappaB activation and reduced the expression of tumor necrosis factor alpha, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase. APC also reduced infarct size and creatine kinase release and improved myocardial left ventricular developed pressure during IR. Conclusions The results of this study indicate that attenuation of NF-kappaB activation and subsequent down-regulation of NF-kappaB-dependent inflammatory gene expression plays an important role in the protective mechanism of APC against acute myocardial IR injury.

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